High Burden Research Articles

Burden of Reintervention after Tetralogy of Fallot Repair: A joint pediatric and adult congenital experience over 30 years

There is a high burden of reintervention after repair of Tetralogy of Fallot (TOF). We compare procedural burden and late outcomes in valve sparing repair (VSR) and transannular patch (TAP) cohorts over 30 years. Patients undergoing TOF repair (1990-2021, excluding complex TOF) were included in this study (n=1239) with subsequent comparisons between TAP (n=550) and VSR (n=648) cohorts. Descriptive statistics, cumulative incidence frequencies, survival analysis and propensity matching (n=425) were used to analyze reintervention burden and survival. Overall survival of the cohort was 96.7% at 15 years and 95.6% at 25 years, with similar survival between TAP and VSR cohorts (p=0.22). TAP cohort had increased incidence of procedural burden at 25 years (TAP 69.8% versus VSR 37.2%, p<0.001), with 34.6% undergoing ≥2 reinterventions. TAP cohort had higher incidence of surgical PV replacement at 15 years (TAP 20.7% versus VSR 7.6%, p<0.001) and placement of PA stents (TAP 20.2% versus VSR 4.9%, p<0.001). By contrast, VSR had higher incidence of RVOT reoperation at 15 years (VSR 7.3% versus TAP 3.6%, p=0.047). After propensity matching there was no survival advantage between the VSR and TAP cohorts (Era 2) whereas the need for RVOT reoperation was not different between the two cohorts (p=0.060). The procedural burden remains high following TOF repair. TAP is associated with higher procedural burden in matched and non-matched cohorts. VSR has increased risk of reoperation for RVOT obstruction only in non-matched comparisons. Anatomical complexity and surgical repair strategy influence procedural burden following TOF repair.

Analysis of the global burden of cardiovascular diseases linked to exposure to ambient particulate matter pollution from 1990 to 2019

BackgroundThis research endeavors to scrutinize the temporal trends and global burden of cardiovascular diseases (CVDs) associated with ambient particulate matter (PM) pollution spanning from 1990 to 2019.MethodsAge-standardized death rates (ASDRs) and age-standardized disability-adjusted life years (DALYs) for CVDs, as well as their estimated annual percentage changes (EAPCs), were calculated using data from the Global Burden of Disease Study 2019 (GBD 2019).ResultsThe global ASDR and age-standardized DALYs due to CVDs associated with PM pollution increased from 1990 to 2019, with a higher increase in males. The burden was higher among middle-aged and older adults. The ASDR and DALYs increased in low-Socio-demographic Index (SDI), low–middle-SDI, and middle-SDI countries, while they decreased in high-SDI countries. The highest burden was observed in Central Asia, North Africa, the Middle East, East Asia, and South Asia. The highest burdens were reported in Iraq, Egypt, and Uzbekistan at the national level.ConclusionThe burden of CVDs linked to PM pollution has grown significantly from 1990 to 2019, with variations across regions and countries, highlighting the need for targeted prevention and pollution management strategies.

The Landscape of Cutaneous T-Cell Lymphoma (CTCL) in the Middle East and North Africa (MENA) and the Establishment of the MENA CTCL Working Group

The high cancer burden in the Middle East and North Africa (MENA region) is coupled with an increasing cancer incidence. While the MENA region constitutes 6% of the world’s population, it remains underrepresented in clinical trials. Cutaneous T-cell lymphomas (CTCLs) represent a heterogeneous group of rare extranodal non-Hodgkin lymphomas with variable clinical presentation. In the MENA region, where darker skin colors are more common than in the West, CTCL generally presents at a younger age and with distinct clinical features that necessitate special expertise and management across disciplines: rare forms of CTCL are more common (hypo- and hyperpigmented MF) and a higher prevalence of pediatric MF is noticed. The multidisciplinary approach to cancer management is growing worldwide and is necessary for the comprehensive management of CTCL. The MENA CTCL group was established with the aim of creating a collaborative environment for the diagnosis and treatment of CTCL in the region. Its first meeting was held in May 2023. The group plans to increase the global representation of the MENA region and establish CTCL registries and patient advocacy groups in the region.

Double burden of gestational diabetes and pregnancy-induced hypertension in Ethiopia: A systematic review and meta-analysis of observational studies.

The coexistence of gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH) amplifies the risk of maternal and perinatal mortality and complications, leading to more severe adverse pregnancy outcomes. This systematic review and meta-analysis aimed to assess the double burden of GDM and PIH (GDM/PIH) among pregnant women in Ethiopia. A comprehensive systematic search was conducted in the databases of PubMed, Cochrane Library, Science Direct, Embase, and Google Scholar, covering studies published up to May 14, 2023. The analysis was carried out using JBI SUMARI and STATA version 17. Subgroup analyses were computed to demonstrate heterogeneity. A sensitivity analysis was performed to examine the impact of a single study on the overall estimate. Publication bias was assessed through inspection of the funnel plot and statistically using Egger's regression test. Of 168 retrieved studies, 15 with a total of 6391 participants were deemed eligible. The pooled prevalence of GDM/PIH co-occurrence among pregnant women in Ethiopia was 3.76% (95% CI; 3.29-4.24). No publication bias was reported, and sensitivity analysis suggested that excluded studies did not significantly alter the pooled prevalence of GDM/PIH co-occurrence. A statistically significant association between GDM and PIH was observed, with pregnant women with GDM being three times more likely to develop PIH compared to those without GDM (OR = 3.44; 95% CI; 2.15-5.53). This systematic review and meta-analysis revealed a high dual burden of GDM and PIH among pregnant women in Ethiopia, with a significant association between the two morbidities. These findings emphasize the critical need for comprehensive antenatal care programs in Ethiopia to adequately address and monitor both GDM and PIH for improved maternal and perinatal health outcomes.

Experience with luspatercept therapy in patients with transfusion-dependent low-risk myelodysplastic syndromes in real-world clinical practice: exploring the positive effect of combination with erythropoietin alfa

BackgroundLuspatercept, an inhibitor of the transforming growth factor beta (TGF-β) pathway, is a novel treatment for anemic patients with lower-risk myelodysplastic syndromes (MDS) with transfusion dependence (TD) who do not respond to erythropoiesis-stimulating agents (ESA) therapy or are not suitable candidates for this treatment. We present real-world experience with luspatercept therapy from two hematology centers in the Czech Republic.MethodsBy January 2024, 54 MDS patients (33 men, 21 women) with a median age of 74 years (range, 55–95) were treated with luspatercept ± ESA at two Charles University hematology centers in Prague and Hradec Králové. According to the WHO 2016 classification, the cohort included 32 MDS-RS-MLD, seven MDS-MLD, two patients with 5q- + ring sideroblasts (RS), 12 RARS-T, and 1 patient with CMML-0 + RS. SF3B1 mutation data were available for 45 patients. All patients were in the IPSS-R and IPSS-M lower-risk groups (except four IPSS-M high). The median follow-up was 17 months (range, 1–54). All patients were transfusion-dependent. Thirty-five (64.8%) patients had a high transfusion burden (HTB) with ≥ 4 transfusion units (TU)/8 weeks, and 19 (35.2%) had a low transfusion burden (LTB) (&amp;lt; 4 TU/8 weeks). The median time between diagnosis and initiation of luspatercept was 27 months (range, 4–156). ESA were used prior to luspatercept in 45 patients, and luspatercept was used as first-line treatment in nine patients. Thirty-one (61%) patients were treated simultaneously with ESA.ResultsOnly patients who received luspatercept for ≥ 8 weeks (51 patients) were assessed. We evaluated the achievement of transfusion independence (TI) lasting 8, 12, 16, and 24 weeks. Thirty-two (62.7%) patients achieved TI for ≥ 8 weeks, 31 (60.7%) for ≥ 12 weeks, 29 (56.8%) for ≥ 16 weeks, and 25 (49%) for ≥ 24 weeks. Hematologic improvement (HI) without TI was achieved in six patients (11.7%). Overall, HI + TI was achieved in 38 patients (74.5%). Epoetin alfa was used simultaneously in 31 patients (60.7%). In 21 (55.2%) of all responding patients, concomitant therapy with epoetin alfa led to an improved response, with 16 reaching TI. Thirteen (25.5%) patients were nonresponders. Eight (21%) patients experienced therapy failure and became transfusion-dependent again. Optimal response required a gradual increase in the luspatercept dose to 1.75 mg/kg in up to 35 patients, with 23 responders (TI + HI). Response rates varied by transfusion burden: 79% in LTB and 50% in HTB reached TI. Of RS+ patients, 70% reached TI, while only one out of five RS− patients achieved TI. Among 39 SF3B1-positive patients, 61.6% achieved TI. In the low and very low IPSS-M groups, 86% of patients responded (TI + HI), compared to 62% in the moderate-low group. Luspatercept was well-tolerated, with no adverse events higher than grade II toxicity.ConclusionWe have demonstrated in real-world clinical practice that luspatercept is a very effective agent, even in an unselected, pretreated, significantly TD MDS population. The effect was particularly high in the IPSS-M low and very low groups. We believe that the relatively high response rate in our patients was influenced by the frequent use of a higher dose (1.75 mg/kg) and especially by adding ESA to luspatercept in poorly responding patients.

HIV incidence and its associated factors among young adults with multiple sexual partners in Maputo, Mozambique: a vaccine preparedness study

IntroductionSub-Saharan Africa has a high burden of HIV, particularly among female sex workers (FSW) and men who have sex with men (MSM). Future clinical trials to evaluate vaccines and other interventions to prevent HIV will need to enroll populations with high HIV incidence. We conducted an observational study of HIV incidence among men and women with multiple sexual partners—including MSM and FSW—in Maputo, Mozambique, in order to prepare the country to conduct future efficacy trials of candidate HIV vaccines and other HIV prevention products.MethodsWe conducted a prospective observational HIV incidence study in Maputo, Mozambique, that enrolled adults aged 18–35 years, without HIV, who had two or more sexual partners in the preceding three months. Recruitment strategies prioritized participation of MSM and FSW. Participants were followed for 24 months with HIV-1 testing every 3 months and staff-administered behavioral questionnaires every 6 months. Cox proportional hazard modeling was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for factors potentially associated with HIV acquisition.ResultsFrom January 2014 to October 2017, 505 adults without HIV were enrolled with median age of 21 years (interquartile range:19–24); 41% were female and 82% were single. There were 19 HIV seroconversions (10 female and 9 male) during 943 person-years (PY) of observation (overall HIV incidence 2.02/100PY; 95%CI 1.21–3.15). The highest HIV incidence was observed among sex workers (2.08/100PY; 95%CI 0.25–7.52) and MSM (19.18/100PY; 95%CI 3.96–56.06). Increased hazard of incident HIV was observed among participants who were MSM (HR = 27.95, 95%CI 4.39–117.94), p = 0.0004), reported three or more sexual partners at enrollment (HR = 7.39, 95%CI 1.64–33.25, p = 0.009), and indicated ever having a sexual partner living with HIV (HR = 9.64, 95%CI 2.23–41.71, p = 0.002).ConclusionOur findings may inform inclusion criteria for upcoming clinical trials of HIV prevention interventions, including vaccine candidates, which may prioritize enrollment of MSM, people with more than three sexual partners, and people with sexual partners who are living with HIV. These same populations are in need of further intervention to reduce HIV incidence.

Fatalism or vigilance? Exposure to infant and maternal deaths and subsequent use of maternal health services in Malawi

In developing contexts, where formal health services are still expanding, understanding what factors discourage individuals from using health services is critical to advance population health. A long theorized, but rarely investigated, conjecture is that in high-mortality contexts, exposure to death can beget fatalism, or even foster distrust of formal healthcare, locking families into cycles of low use of health services. A counter perspective, however, suggests exposure to death can encourage individuals’ health vigilance, corresponding with their higher use of health services. We test these competing ideas by analyzing the associations between women’s intimate exposure to death in the context of pregnancy and delivery via (1) a sister’s maternal death and (2) an infant child’s neonatal death, and their subsequent use of maternal health services. We focus on the context of Malawi, a setting that features high maternal and infant mortality rates, similar to those observed across much of sub-Saharan Africa, as well as persistent gaps in service use. Specifically, we use Malawi Demographic and Health Survey (2015–16) data to examine if a sister’s maternal death or a child’s neonatal death corresponds with a woman’s odds of attending full antenatal care during a subsequent pregnancy or delivering the pregnancy at a formal health facility. Given the qualitatively distinct nature of losing one’s only or first child, we also assess if the effect of a child’s neonatal death varies by birth order. The results show that maternal and neonate death exposures correspond generally with women’s higher use of maternal health services, challenging the notion that exposure to death fosters fatalism or distrust. Although the results vary in significance, the nuanced findings highlight women’s vigilance in the face of health threats, emphasizing their resilience amid a high burden of familial loss.

A Monte Carlo study comparing dead-time losses of a gamma camera between tungsten functional paper and lead sheet for dosimetry in targeted radionuclide therapy with Lu-177.

Dead-time loss is reported to be non-negligible for some patients with a high tumor burden in Lu-177 radionuclide therapy, even if the administered activity is 7.4GBq. Hence, we proposed a simple method to shorten the apparent dead time and reduce dead-time loss using a thin lead sheet in previous work. The collimator surface of the gamma camera was covered with a lead sheet in our proposed method. While allowing the detection of 208-keV gamma photons of Lu-177 that penetrate the sheet, photons with energies lower than 208keV, which cause dead-time loss, were shielded. In this study, we evaluated the usefulness of tungsten functional paper (TFP) for the proposed method using Monte Carlo simulation. The count rates in imaging of Lu-177 administered to patients were simulated with the International Commission on Radiological Protection (ICRP) 110 phantom using the GATE Monte Carlo simulation toolkit. The simulated gamma cameras with a 0.5-mm lead sheet, 1.2-mm TFP, or no filter were positioned closely on the anterior and posterior sides of the phantom. The apparent dead times and dead-time losses at 24h after administration were calculated for an energy window of 208keV ± 10%. Moreover, the dead-time losses at 24-120h were analytically assessed using activity excretion data of Lu-177-DOTATATE. The dead-time loss without a filter was 5% even 120h after administration in patients with a high tumor burden and slow excretion, while those with a lead sheet and TFP were 0.22 and 0.58 times less than those with no filter, respectively. The count rates with the TFP were 1.3 times higher than those with the lead sheet, and the TFP could maintain primary count rates at 91-94% of those without a filter. Although the apparent dead time and dead-time loss with the lead sheet were shorter and less than those with TFP, those with TFP were superior to those without a filter. The advantage of TFP over the lead sheet is that the decrease in primary count rates was less.

Long-Term control with immunotherapy and aggressive re-irradiation for basal cell carcinoma metastatic to the vertebra: A case report and literature review of rare osseous metastasis

BackgroundCutaneous basal cell carcinoma (BCC) is a prevalent malignancy with a rising incidence, though it rarely metastasizes, with an incidence of 0.0028% to 0.5%. Hematogenous metastatic BCC (mBCC) is particularly rare and associated with a median survival of 8-14 months. Case DetailsThis case report details a 59-year-old male with a primary BCC on his left shoulder metastasizing to the lungs and spine. Despite aggressive multimodal treatment, including surgery, radiation, and systemic therapy with hedgehog inhibitors (vismodegib, sonidegib), the disease progressed. At 55 months post-diagnosis, pembrolizumab was introduced due to the high tumor mutation burden (TMB-H), resulting in a notable therapeutic response and prolonged survival. The patient underwent extensive follow-up, including re-irradiation of spinal metastases and immunotherapy, maintaining stable disease for over 101 months. Results/Literature ReviewA systematic literature review identified only 26 cases of osseous mBCC, primarily treated with surgery and radiation, with variable survival outcomes. This case stands out due to its prolonged survival and novel use of pembrolizumab, highlighting the potential role of immunotherapy in TMB-H mBCC. The patient’s TMB-H status likely contributed to the favorable response to immunotherapy. ConclusionThis report underscores the importance of genetic profiling in mBCC to identify candidates for emerging immunotherapy treatments. The findings suggest that patients with high mutational burden mBCC may benefit from pembrolizumab, offering a new therapeutic avenue for this rare osseous metastasis.

Unbiased temperature-related mortality estimates using weekly and monthly health data: a new method for environmental epidemiology and climate impact studies.

Exposure to environmental factors has a high burden on human health, with millions of premature annual deaths associated with the short-term health effects of ambient temperatures and air pollution. However, direct estimations of exposure-related mortality from real data are still not available in most parts of the world, especially in low-resource settings, due to the unavailability of daily health records to calibrate epidemiological models. In this study, we have filled the crucial gap in available direct estimations by developing a method to make valid inference for the relationship between exposure and response data that uses only exposure and temporally aggregated response data. We provided the mathematical derivation of the method, and compared the results by using simulations applied to daily temperature and daily, weekly, and monthly mortality data. The method was then applied to the newly created database of the EARLY-ADAPT project. The daily and weekly models produced similar and unbiased estimates of the temperature-related relative risks and attributable mortality, with only slightly more imprecision in the weekly model. Even the estimates of the monthly model were unbiased when using enough data, although at the expense of a substantial increase in variability. The real data analysis showed that the similarity between the regional values of two aggregation models increased with the number of years and regions of the dataset, and decreased with the difference in their degree of temporal aggregation. Our method opens the door to conducting epidemiological studies in low-resource settings, where access to daily health data is not possible. Moreover, it allows accurate estimation of the short-term health effects of environmental exposures in near-real time, when daily health data are still not available, such as in the estimation of the mortality burden of recent record-breaking heat episodes. Overall, our method represents an important new approach to how the public health community can use data to create new evidence for research, translation and policy making. European Research Council (ERC).

Assessing the Burden of Atopic Dermatitis in Portugal through Patient-Centered Experiences

Introduction: Adult patients and caregivers of children with atopic dermatitis experience high physical, mental, and financial burden in Portugal. We outline the experience of atopic dermatitis management and how the current medical care model impacts patient-centered concerns such as financial burden, quality of life, disease burden, and treatment satisfaction. Methods: We conducted a survey of 419 Portuguese adults and caregivers of children to capture the experience of managing atopic dermatitis in Portugal. Results: Respondents reported average satisfaction with treatment, with a mean satisfaction rating of 3.15/5.00 (SD = 0.77). Adults reported slightly better control of atopic dermatitis symptoms (mean = 56.6) than pediatric patients (mean = 55.9, caregiver reported). Nearly 34% of adults and 39% of caregivers of children and adolescents indicated that their healthcare providers asked about their priorities at the last medical visit. Additionally, only 40% of adult patients and 32% of caregivers reported that patient training was offered to them. Respondents seeing dermatologists reported higher satisfaction than those seeing other healthcare providers (p = 0.01) but there were no differences in long-term control of symptoms by provider type (p = 0.85) when controlling for severity. Portuguese adult patients scored 0.86/1.00 on the EQ-5D (where 0 = death and 1 = perfect health). Financial concern was high as nearly 80% of patients and caregivers reported using savings, borrowing money, and/or reducing spending to cover atopic dermatitis-related costs.Conclusion: Portuguese patients with atopic dermatitis and caregivers experience financial burden, lower health-related quality of life, higher disease burden, and treatment satisfaction issues with their current medical care. These factors often deteriorate as the disease’s severity increases. Providers, researchers and policymakers should focus on better addressing patient-centered concerns for individuals suffering from atopic dermatitis to improve care and health outcomes.

Immune-related glycosylation genes based classification predicts prognosis and therapy options of osteosarcoma

Osteosarcoma is the most common primary bone malignancy, with a very poor prognosis. Aberrant glycosylation is close involvement in osteosarcoma. Accordingly, this study aimed at investigating the role of glycosylation genes in the prognosis and therapy options of osteosarcoma. The microenvironment of osteosarcoma was assessed using estimate algorithm. A total of 20 immune-related glycosylation genes (IRGGs) was identified using Pearson correlation analysis. Accordingly, osteosarcoma patients were divided into C1 and C2 type using consensus clustering. Multiple algorithms (Xcell, MCP-counter, ssGSEA, epic, quantiseq), cancer immune cycle analysis, and GSVA were applied to estimate the immune, molecule and metabolism characteristics of osteosarcoma, indicating that C1 type was featured with high immune infiltration, high glycosylation, enriched MEK signaling, and good prognosis, while C2 type was characterized by more metastasis, enriched immunotherapy-positive gene signatures, high tumor mutation burden, and poor prognosis. Results from TIDE algorithm and immunotherapy datasets suggested the C2 type’s preference of immune checkpoint inhibitors (ICIs), while data of GDSC, CMap analysis and cell experiments indicated that C1 type was sensitivity to MEK inhibitor PD0325901. In addition, univariate Cox and Lasso analysis was combined to establish an IRGGs’ risk score containing 6 genes (B3GNT8, FUT7, GAL3ST4, GALNT14, HS3ST2, and MFNG). The data of DCA and ROC indicated its well prediction of prognosis in osteosarcoma. Finally, cellular location analysis showed that the 6 genes not only distributed in tumor cells but also in immune cells. In summary, the classification and risk score based on IRGGs effectively predicted the prognosis and therapy options of osteosarcoma. Further studies on IRGGs may contribute to the understanding of cancer immunity in osteosarcoma.

CAR-redirected natural killer T cells demonstrate superior antitumor activity to CAR-T cells through multimodal CD1d-dependent mechanisms.

Human natural killer T (NKT) cells have been proposed as a promising cell platform for chimeric antigen receptor (CAR) therapy in solid tumors. Here we generated murine CAR-NKT cells and compared them with CAR-T cells in immune-competent mice. Both CAR-NKT cells and CAR-T cells showed similar antitumor effects in vitro, but CAR-NKT cells showed superior antitumor activity in vivo via CD1d-dependent immune responses in the tumor microenvironment. Specifically, we show that CAR-NKT cells eliminate CD1d-expressing M2-like macrophages. In addition, CAR-NKT cells promote epitope spreading and activation of endogenous T cell responses against tumor-associated neoantigens. Finally, we observed that CAR-NKT cells can co-express PD1 and TIM3 and show an exhaustion phenotype in a model of high tumor burden. PD1 blockade as well as vaccination augmented the antitumor activity of CAR-NKT cells. In summary, our results demonstrate the multimodal function of CAR-NKT cells in solid tumors, further supporting the rationale for developing CAR-NKT therapies in the clinic.

NLRP3 inflammasome-induced pyroptosis and serum ASC specks are increased in patients with cardiogenic shock.

Cardiogenic shock (CS) is characterized by impaired cardiac function, very high mortality, and limited treatment options. The proinflammatory signaling during different phases of CS is incompletely understood. We collected serum and plasma (n = 44) as well as freshly isolated peripheral blood mononuclear cells (PBMCs, n = 7) of patients with CS complicating acute myocardial infarction on admission and after revascularization (24, 48, and 72 h) and of healthy controls (serum and plasma, n = 75; PBMCs, n = 12). PBMCs of patients with CS had increased gene expression of NLRP3, CASP1, PYCARD, IL1B, and IL18 and showed increased rates of pyroptosis (control, 4.7 ± 0.3 vs. 9.9 ± 1.7% in patients with CS, P = 0.02). Serum interleukin (IL)-1β levels were increased after revascularization. IL-18 and IL-6 were higher in patients with CS than in healthy controls but comparable before and after revascularization. Proinflammatory apoptosis-associated speck-like proteins containing CARD (ASC) specks were elevated in the serum of patients with CS on admission and increased after revascularization (admission, 11.1 ± 4.4 specks/µL; after 24 h, 19.0 ± 3.9, P = 0.02). ASC specks showed a significant association with 30-day mortality in patients with CS (P < 0.05). The estimated regression coefficients and odds ratios indicated a positive relationship between ASC specks and mortality (odds ratio: 1.029, 95% confidence interval, 1.000 to 1.072; P = 0.02). Pyroptosis and circulating ASC specks are increased in patients with CS and are particularly induced after reperfusion. This underscores their potential role as a biomarker for poor outcomes in patients with CS. ASC specks represent promising new therapeutic targets for patients with CS with high inflammatory burden.NEW & NOTEWORTHY The expression of NLR family pyrin domain containing-3 (NLRP3) inflammasome-related genes and the rate of pyroptosis are increased in PBMCs from patients with CS. Furthermore, patients with CS are characterized by higher serum concentrations of ASC specks and IL-1β, IL-6, and IL-18. This current study adds circulating ASC specks to the portfolio of biomarkers for the identification of patients with a high inflammatory burden paving the way for precision medicine approaches to improve clinical outcomes.

Effect of streamlining prior authorization processes for systemic cancer treatments on efficiency and financial losses.

412 Background: Prior authorizations (PAs) for systemic cancer treatments are a barrier to timely quality cancer care delivery. The high administrative burden to complete peer to peer’s (P2P) and appeals leads to care delays and revenue losses. At our tertiary academic cancer center, in partnership with our cancer registry and Epic teams, we shifted the clerical work required for PAs from clinicians to certified tumor registrars (CTRs) to increase authorization efficiency and decrease financial losses from denials. Methods: Clinicians place the treatment plan order which goes to the CTR work queue. We leveraged the Epic staging smart form to consolidate and auto-populate common elements needed for PA. The CTRs then complete and validate the form prior to the authorization specialists obtaining the PA. We compared the pre (1/2022-9/2022) and post-implementation (11/2022-4/2024) periods on our primary outcomes: average monthly number of PAs pending review (including P2P, appeals and authorizations requiring clarifying clinical documentation), average monthly denial rate and average time spent on PAs by the authorization specialists. We compared the financial losses from denied PAs from calendar year 2022 to 2023. Analyses were conducted using descriptive statistics. Results: There was a 1.4% reduction in the average monthly number of PA’s pending review (350 vs 345). The average monthly authorized rate was steady from the beginning of the intervention (94%) to present time (95%). The average monthly denial rate was 2.9% at the beginning of the intervention and 0.9% at present time. There was a consistent decrease in the average time a PA was spent in pending review status: 118 hours in 2022, 102 hours in 2023 and 79 hours in quarter 1 of 2024. Despite the overall increase in volume of authorizations submitted, there was an overall cost savings of $27,392,894 from 2022 ($49,964,703) to 2023 ($22,571,809) from the decrease in denials. In 2022, 6.2% of total approved charges were denied and this decreased to 2.7% in 2023. Conclusions: By leveraging the EHR and optimizing existing non-clinical staff workflows, we maintained sustained average authorized and denial rates despite overall volume going up due to improved authorization efficiency and reduced financial losses due to denials. Additionally, there were overall cost savings for the institution due to the decreased percent of denials of total approved charges. Future work will include further refinement of treatment and disease specific optimizations.

Effects of Social Vulnerability and Environmental Burden on Care Fragmentation and Social Needs Among Individuals With Rheumatic Conditions.

Environmental hazards and heightened neighborhood social vulnerability coexist and disproportionately affect minoritized populations. We investigated associations between exposure to adverse environmental burden concentrated in areas with high social vulnerability and care fragmentation (missed appointments, emergency department visits, and hospitalizations) and social needs (eg, food and housing insecurity) among individuals with rheumatic conditions. We identified adults receiving care in a Massachusetts multihospital system with at least two rheumatic disease codes and complete street addresses. Geocoded addresses were linked to the Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry Social-Environmental Ranking (SER), which combines census-tract social vulnerability variables (eg, socioeconomic status) with environmental hazards (eg, air and water pollution). Social needs were obtained from self-reported surveys. Multilevel, multinomial regression models estimated associations between SER quartiles and care fragmentation and social need burden, accounting for demographics and comorbidities. Among 16,856 individuals with rheumatic conditions, 70% were female, 6% were Black, 82% were White, and 7% resided in the highest combined social vulnerability and environmental burden (SER quartile 4) areas. Among 7,083 with social needs data, 19% experienced more than one challenge. Individuals in SER quartile 4 areas (vs quartile 1) had 2.02 (95% confidence interval [CI] 1.67-2.46) times greater odds of at least four care fragmentation occurrences (vs 0) and 2.37 (95% CI 1.73-3.25) times greater odds of at least two social needs (vs 0). Residence in areas of high combined adverse environmental burden and social vulnerability was associated with significantly greater odds of care fragmentation and social needs. Addressing structural factors and emerging environmental threats contributing to these adverse exposures is essential to reduce rheumatic disease care inequities.

An updated comparative analysis of needs and role of patient navigation among early phase cancer clinical trial participants and non-participants at a single cancer center.

237 Background: Early phase clinical trials (EPCTs) assess the safety and toxicity of novel anticancer agents and represent opportunities for patients (pts) to try novel therapies when standard therapies have become ineffective. However, EPCT participants represent a vulnerable population with high financial toxicity and symptom burdens. EPCTs may add to these burdens by requiring frequent, long visits and additional procedures. Pt navigators perform needs assessments and provide guidance to pts as they move through the health care system. Navigation, which has a high level of acceptance among pts with cancer, can improve time from diagnosis to treatment, decrease pt anxiety, and improve participation of minoritized individuals in clinical trials. We hypothesized that EPCT participants would have higher navigation needs than those of non-EPCT participants with cancer. Methods: Utilizing a needs assessment conducted in person or by telephone, pts with cancer treated at Mount Sinai are assessed for 26 individual and systemic social drivers of health (SDoH) barriers by pt navigators at their trial screening visit. EPCT participants were defined as pts participating in a study in the Early Phase Trials Unit. Descriptive characteristics were assessed for all participants regarding demographic characteristics and SDoH barriers. Welch's T-test was used to compare differences in navigation encounters and SDoH barriers between the EPCT and non-EPCT pt groups. Results: From February 2023 to April 2024, 40 EPCT pts and 1290 non-EPCT pts completed the assessment. Median age was 60.5 and 63.1 years, respectively. Racial and ethnic self-identification included 17.5% vs. 19% Black pts and 10% vs. 17% Hispanic pts. EPCT pts had a mean 5.2 navigation encounters per pt compared to 3.05 in non-EPCT pts (p=0.002). Pts in the EPCT group were found to have an average of 2.8 SDoH barriers identified, in contrast to 2.0 in the non-EPCT group (p=0.002). The most common barriers identified in EPCT pts were institutional, knowledge, psychosocial and financial; in non-EPCT pts, transportation, institutional, knowledge and treatment adherence were most common. Interventions related to institutional barriers most frequently involved coordinating with the primary team and among departments. Interventions related to knowledge included providing education and teach back. Conclusions: EPCT pts had more SDoH barriers identified, higher acuity of barriers, and required more navigation encounters than non-EPCT pts. Participants in EPCTs are a vulnerable pt population for whom navigation is particularly warranted. EPCT pts Non-EPCT pts p value Navigation encounters, mean (SD) 5.20 (6.16) 3.05 (4.34) 0.002 SDoH barriers identified, mean (SD) 2.82 (1.83) 2.00 (1.66) 0.002

Do Collaterals to Infarct Bed in STE-ACS Patients Undergoing Emergent Percutaneous Coronary Revascularization Matter? An Assessment of a Prospective Pool for In-Hospital Course

Limited data exist on the role of coronary collaterals circulation (CCC) in patients with ST-elevation acute coronary syndrome (STE-ACS). This study aimed to assess CCC and the in-hospital course of patients with CCC undergoing primary percutaneous coronary intervention (pPCI). The study included consecutive STE-ACS patients undergoing pPCI. Good CCC was defined as Rentrop collateral score (RCS) of 2-3. Patients with good and poor CCC were compared regarding clinical characteristics, angiographic patterns, and hospital course. In the sample of 4,683 patients, mean age was 55.6±11 years, and 78.8% were male. Good CCC was observed in 499 (10.7%) patients. The rate of intra-procedure slow-flow/no-reflow (SF/NR) was 29.9% vs. 20.5% (p<0.001), and the rate of composite adverse clinical outcomes (CACO) was 21.2% vs. 19% (p=0.225) for patients with good and poor CCC, respectively. Multivariable analysis identified left ventricular end-diastolic pressure (LVEDP), multi-vessel disease (MVD), and thrombus grade ≥4 as independent predictors of good CCC, with adjusted odds ratios of 0.98 [0.97-0.99], 1.69 [1.35-2.10], and 3.45 [2.64-4.52], respectively. In propensity-matched cohorts, the intra-procedure SF/NR rate was 29.9% vs. 26.9% (p=0.292), and the rate of CACO was 21.2% vs. 23.4% (p=0.403) for patients with good and poor CCC, respectively. Angiographic evidence of good CCC in STE-ACS patients was limited. Good CCC was associated with a higher prevalence of MVD, high thrombus burden, and low pre-procedure LVEDP, resulting in a higher incidence of intra-procedure SF/NR. However, the CACO did not differ significantly between patients with good and poor CCC.

Isoniazid resistance pattern among pulmonary tuberculosis patients in Bangladesh: an exploratory study

ObjectivesIn high TB burden countries like Bangladesh, research and policies tend to focus on rifampicin (RIF)-resistant TB patients, leaving RIF sensitive but isoniazid (INH) resistant (Hr-TB) patients undiagnosed. Our study aims to determine the prevalence of INH resistance among pulmonary TB (PTB) patients in selected healthcare facilities in Bangladesh. MethodsThis study was conducted across nine TB Screening and Treatment Centers situated in Bangladesh. Sputum samples from 1084 Xpert-positive PTB patients were collected between April 2021 and December 2022, and cultured for drug susceptibility testing (DST). Demographic and clinical characteristics of Hr-TB and drug-susceptible TB patients were compared. ResultsAmong available DST results of 998 culture positive isolates, resistance rate of any INH regardless of RIF susceptibility was 6.4% (64/998, 95% CI, 4.9-8.2). The rate was significantly higher in previously treated (21.1%, 16/76, 95% CI, 12.0-34.2) compared to newly diagnosed TB patients (5.2%, 48/922, 95% CI, 3.8-6.9) (p <0.001). The rate of Hr-TB was 4.5% (45/998, 95% CI, 3.3-6.0), which was also higher among previously treated (6.6%, 5/76, 95% CI, 1.4-13.5) compared to newly diagnosed TB patients (4.3%; 40/922, 95% CI, 3.1-5.9) (p=0.350). Most importantly, the rate of Hr-TB was more than double compared to MDR-TB (4.5%, 45/998, vs 1.9%, 19/998) found in the current study. ConclusionsThis study reveals a high prevalence of Hr-TB, surpassing even that of the MDR-TB in Bangladesh. This emphasizes the urgent need to adopt WHO-recommended molecular tools at the national level for rapid detection of INH resistance so that patients receive timely and appropriate treatment.

Cachexia in tuberculosis in South-East Asian and African regions: knowledge gaps and untapped opportunities.

Tuberculosis (TB) and cachexia are clinical entities that have a defined relationship, making them often found together. TB can lead to cachexia, while cachexia is a risk factor for TB. This article reviews cachexia in Tuberculosis patients in Southeast Asian and African regions by conducting a comprehensive literature search across electronic databases such as PubMed, Google Scholar, and Research Gate between 2013 and 2024 using keywords including 'Africa', 'cachexia', 'prevalence', 'implications', 'tuberculosis', and 'Southeast Asia. This article utilized only studies that satisfied the inclusion criteria, revealing knowledge gaps and untapped opportunities for cachexia in TB across Southeast Asian and African regions. Many Southeast Asian and Western Pacific patients initially receive a tuberculosis diagnosis. Sub-Saharan African countries are among the 30 high TB burden nations, according to the WHO. Food inadequacy and heightened energy expenditure can impair the immune system, leading to latent TB and subsequently, active infection. Symptoms needing attention: shortness of breath, productive cough, hyponatremia at 131mmol/l, hypoalbuminemia at 2.1g/dl, elevated aspartate transaminase at 75U/l, increased lactate dehydrogenase at 654, and normocytic anemia. Comorbidities, such as kidney disease, cardiovascular disease, and asthma, can influence the nutritional status of individuals with TB. While efforts like screening, contact tracing, and utilizing gene Xpert to detect TB cases were implemented, only a few proved effective. It is essential to conduct further studies, including RCTs, in Southeast Asia and Africa to evaluate and manage cachexia in TB patients.